Dichotomy of CCL21 and CXCR3 in nerve injury-evoked and autoimmunity-evoked hyperalgesia.

The chemokine CCL21 is released from injured neurons and acts as a ligand of the chemokine receptor, CXCR3, which likely contributes to pro-inflammatory adaptations and secondary neuronal damage. CCL21-CXCR3 signalling may therefore impact on the development of neuropathic pain. By using the respective knockout mice we show that deficiency of CCL19/21 in plt/plt mice attenuates nerve injury evoked pain but not the hyperalgesia evoked by autoimmune encephalomyelitis (EAE).

Inter-strain differences of serotonergic inhibitory pain control in inbred mice.

Background: Descending inhibitory pain control contributes to the endogenous defense against chronic pain and involves noradrenergic and serotonergic systems. The clinical efficacy of antidepressants suggests that serotonin may be particularly relevant for neuropathic pain conditions. Serotonergic signaling is regulated by synthesis, metabolisms, reuptake and receptors.

R-flurbiprofen reduces neuropathic pain in rodents by restoring endogenous cannabinoids.

Background: R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear.

Methodology/principal Findings: We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice.

Inhibitor kappaB Kinase beta deficiency in primary nociceptive neurons increases TRP channel sensitivity.

Inhibitor kappaB kinase (IKK) regulates the activity of the transcription factor nuclear factor-kappa B that normally protects neurons against excitotoxicity. Constitutively active IKK is enriched at axon initial segments and nodes of Ranvier (NR). We used mice with a Cre-loxP-mediated specific deletion of IKKbeta in sensory neurons of the dorsal root ganglion (SNS-IKKbeta(-/-)) to evaluate whether IKK plays a role in sensory neuron excitability and nociception.